Download The role of echocardiography in guiding management in dilated

European Journal of Echocardiography (2009) 10, iii15–iii21
doi:10.1093/ejechocard/jep158
The role of echocardiography in guiding management
in dilated cardiomyopathy
Dewi E. Thomas, Richard Wheeler, Zaheer R. Yousef, and Navroz D. Masani*
Department of Cardiology, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK
KEYWORDS
Dilated cardiomyopathy;
Echocardiography;
Diagnosis;
Prognosis;
Treatment
Dilated cardiomyopathy (DCM) is a common and malignant condition, which carries a poor long-term
prognosis. Underlying disease aetiologies are varied, and often carry specific implications for treatment
and prognosis. The role of echocardiography is essential in not only establishing the diagnosis, but also in
defining the aetiology, and understanding the pathophysiology. This article therefore explores the
pivotal role of echocardiography in the evaluation and management of patients with DCM.
Introduction
Diagnosis and differential diagnosis
There are many different causes of DCM but in most cases it
is unknown, i.e. idiopathic. The clinical presentation of all
* Corresponding author. Tel: þ44 292 074 4086; fax: þ44 292 074 3916.
E-mail address: [email protected]
Idiopathic dilated cardiomyopathy
The prevalence of idiopathic dilated cardiomyopathy is not
well understood but an estimate in the USA is 40 per
100 000 persons.2 Genetic factors are important with more
than 25% of cases having a familial basis which is normally
autosomal dominant.3 This has important implications for
screening of first-degree relatives.
The hallmark of the disease is LV dilatation and/or dysfunction. Dilatation may precede dysfunction in many
cases, and therefore attention to accurate chamber
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2009.
For permissions please email: [email protected].
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Dilated cardiomyopathy (DCM) is a primary myocardial
disease characterized by varying degrees of left ventricular
(LV) dysfunction and dilatation in the absence of chronic
increased afterload (e.g. aortic stenosis or hypertension),
or volume overload (e.g. mitral regurgitation, MR). Historically, the prognosis of patients with DCM has been very
poor, with a median survival of two years after diagnosis,1
and although there have been advances in the medical and
surgical therapy of DCM in the last two decades, the condition still carries a very poor long-term prognosis.
In patients with suspected heart failure or LV dysfunction,
echocardiography is the most important investigation in
establishing the diagnosis of DCM, by defining the presence
and severity of LV dilatation and dysfunction. Diagnostic criteria have relied on the identification of an ejection fraction
(EF) ,45%, and/or a fractional shortening ,25%, in association with a LV end-diastolic dimension .112% predicted
value corrected for age and body surface area. Echocardiography, however, not only facilitates evaluation of strict diagnostic criteria, but also provides us with a powerful tool with
which to make a comprehensive assessment of cardiac
anatomy, pathophysiology, and haemodynamics. In this
article, we describe the role of echocardiography in guiding
the management of DCM: (i) establishing an accurate and
complete diagnosis, (ii) identifying high-risk features and predicting prognosis, (iii) guiding therapeutic interventions.
cases should prompt a thorough evaluation of the patient
in order to define the exact aetiology. This is of critical
importance in terms of establishing a precise diagnosis,
assessing prognosis, and guiding management and serves as
a reminder that many different cardiac diseases will have
a ‘DCM phenotype’.
Echocardiography has a unique role in accurately defining
the condition, establishing the diagnosis in patients presenting with heart failure, not least by identifying other cardiac
diagnoses, e.g. coronary artery disease and valvular
disease. A detailed description of the echocardiographic features of all of the conditions causing a ‘secondary’ DCM-like
picture is beyond the remit of this article, however, the
main differential diagnoses in DCM (3) are shown in Table 1,
along with the key clinical and echocardiographic features.
Each of these conditions has specific associated features,
often coupled with unique prognostic and therapeutic implications. For example, recognition of the echocardiographic
and haematological features of hypereosinophilic heart
disease can guide management with immunosuppressant
therapy and anticoagulation, resulting in complete resolution
of the myocardial disease state in the absence of serious
clinical sequelae (Figure 1).
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D.E. Thomas et al.
Table 1 Differential diagnosis in dilated cardiomyopathy
Diagnosis
Key echo features
Idiopathic dilated cardiomyopathy
Ischaemic heart disease
Hypertension
Severe valvular disease
Infiltrative disease
Amyloid
Sarcoidosis
Haemochromatosis
Myocarditis
Hypereosinophilic syndrome
The classical phenotype—varying degrees of dilatation and dysfunction
Regional wall motion abnormalities, scar, aneurysm formation
Left ventricular hypertrophy
Valve abnormalities
Connective tissue disease
Toxins—alcohol, cocaine, chemotherapy, e.g.
doxorubicin, trastuzumab
Endocrine
Thyroid disease
Phaeochromocytoma
Acromegaly
Carcinoid
Neuromuscular disease
None specific
Left ventricular hypertrophy
Left ventricular hypertrophy
Characteristic valvular abnormalities
Left ventricular hypertrophy
Posterior wall motion abnormality in Friedrich’s ataxia
Regional wall motion abnormalities
Characteristic rheumatic change in valves
None specific
Increased trabeculation of the endocardium with deep sinusoids
None specific
Apical hypokinesia/akinesia with preservation of the basal segments
Variable depending upon associated structural abnormalities
Adapted from Felker et al. N Engl J Med 2000;342;1077–84.
Figure 1 Hypereosinophilic heart disease in a young woman with heart failure. Upper panels: echocardiography at presentation shows
extensive, echogenic thrombus adherent to the endocardium in the apical four chamber (left) and long-axis (right) views. Investigation
revealed a primary eosinophilia. Lower panels: after treatment with prednisolone, azathioprine, warfarin, and heart failure therapies,
there is resolution of thrombus, reduction in LV size, and improvement in LV function.
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Radiation
Rheumatic carditis
Neoplastic disease
Left ventricular non-compaction
Peripartum cardiomyopathy
Takotsubo cardiomyopathy
Congenital heart disease
Thickened myocardium, small pericardial effusion
Nodules, focal aneurysms
Thickened myocardium, abnormal myocardial texture
None specific, small pericardial effusion
Endomyocardial echogenicity indicating fibrosis particularly affecting the posterior wall
Laminar thrombus attached to endocardium often at the apex
Valve abnormalities, aortic dilatation
None specific
Echocardiography in guiding management in DCM
dimensions, indexed according to body surface area,4 is
important. This is of particular relevance in the long-term
follow-up of DCM patients, in order to comment on disease
progression or response to treatments.
A comprehensive analysis of regional, as well as global,
systolic function is of vital importance in establishing the
diagnosis. The presence of regional wall motion abnormalities in a recognized coronary distribution is highly suggestive of ischaemic cardiomyopathy, and the additional
finding of echo bright, thinned myocardium provides
further substantive evidence of a prior myocardial infarct.
However, it is equally important to note that these features
often appear far more subtle when assessing a globally poor
ventricle which may have undergone adverse remodelling
following myocardial infarction. It is also important to
recognize that in many forms of non-ischaemic DCM (including idiopathic) the basal posterolateral segments often
appear to have relatively preserved systolic function, but
this ‘regionality’ should not lead to the assumption of coronary disease.
Valve disease
merit specific consideration in the differential diagnosis of
the DCM phenotype.
Left ventricular non-compaction
LVNC is characterized by prominent trabeculations on the
endocardial surface of the LV with deep recesses extending
into the LV wall (Figure 2). LV function may be severely
decreased and the appearance can be similar to any cause
of DCM. LVNC can occur in isolation or in association with
other congenital defects such as Ebstein’s anomaly. LVNC is
often familial with an autosomal dominant mode of inheritance and also carries with it a high risk of mural thrombosis
(within the recesses), ventricular arrhythmia, sudden
cardiac death. Establishing the diagnosis therefore carries
major implications in terms of family screening, anticoagulation, and protective device therapy. Unfortunately,
however, it is felt that the current diagnostic criteria are
too sensitive and have led to a significant over diagnosis of
the condition.5 In patients with DCM of any cause the
dilated ventricle may allow the endocardium to be seen in
detail, particularly in a good echo subject, and this can
lead to over interpretation of what is LV trabeculation
within the spectrum of normality.
Takotsubo cardiomyopathy
Takotsubo cardiomyopathy was first described in Japan in
20016 and is also known as transient LV apical ballooning or
‘broken heart’ syndrome. It usually presents with typical
chest pain often precipitated by severe emotional stress.
The ECG will show anterior ischaemic changes with a small
rise in cardiac enzymes but with normal coronary angiography. The echocardiographic appearance is of apical and/or
mid-LV hypokinesia or akinesia often with hyperkinesia of
the basal segments. Importantly, this condition is reversible
within days or weeks which completes the diagnostic
process.
Assessing prognosis in dilated cardiomyopathy
Unclassified cardiomyopathies
Left ventricular non-compaction (LVNC) and Takotsubo cardiomyopathy fall into the category of unclassified cardiomyopathy according to the European classification. They
All patients with DCM will undergo echocardiography as part
of their initial investigation. In addition to its pivotal role in
diagnosis, echocardiography should be used to identify highrisk features and predict prognosis. A number of clinical and
Figure 2 Left ventricular non-compaction. (A) There is marked LV dilatation and dysfunction, thinning of the septum and hypertrophy,
excessive trabeculation of the lateral wall and apex. (B) Colour flow mapping shows flow within deep recesses, extending to the epicardium
at the apex.
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Chronic LV volume or pressure overload due to valvular pathology will eventually lead to dilatation and dysfunction. It is
crucially important to identify valvular pathology given the
obvious management implications, i.e. corrective surgery.
In particular, a small proportion of patients with aortic
stenosis will present with overt heart failure symptoms in
the setting of severely impaired LV function. There is a
risk of underestimating the severity of aortic stenosis due
to the phenomenon of low flow/low gradient aortic stenosis.
A thorough assessment of valve morphology will therefore
help to avoid this pitfall, taking particular note of bicuspid
aortic valve disease which may have relatively preserved
motion of the body of the leaflets leading to underestimation of the degree of aortic stenosis. MR is considered
later in this article.
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D.E. Thomas et al.
Table 2 Clinical and echocardiographic indicators of prognosis in dilated cardiomyopathy
Prognostic indicator
Key echocardiographic features
Aetiology
Arrhythmias
LV size and systolic function
LV diastolic function
Exercise capacity
Neurohormonal status
Right ventricular function
Pulmonary hypertension
Left atrial size
Mitral regurgitation
Contractile reserve
(See Table 1)
echocardiographic indicators of prognosis have been established. These are summarized in Table 2.
Left ventricular size and systolic function
TAPSE
Tricuspid regurgitation velocity
Left atrial volume index
Presence, severity, mechanism
Dobutamine stress echo
echocardiographic assessment of DCM should include
methods of identifying the pseudonormal pattern, such as
tissue-Doppler analysis of the mitral annulus (E0 velocity),
pulsed-wave Doppler of pulmonary venous inflow and left
atrial size, in order to fully define the category of diastolic
dysfunction.
Diastolic filling period (normally 60% of the cardiac
cycle) is reduced in some patients with DCM. This may be
sign of atrioventricular dyssynchrony and results in
reduced stroke volume as well as increased left atrial
pressure, which may be further exacerbated by pre-systolic
MR. Identification of these two phenomena requires careful
assessment of mitral inflow and regurgitation by pulsed- and
continuous-wave Doppler. This information is important in
guiding cardiac resynchronization therapy (CRT) and, in particular, atrioventricular optimization.
Right ventricular dysfunction
RV dysfunction may be present in DCM and is an important
adverse prognostic marker,15 associated with significantly
worse functional class and outcome. It appears to be
related to the severity of LV dysfunction and biventricular
involvement in the disease process rather than secondary
to pulmonary hypertension.16 Quantification of right ventricular function is technically difficult due to its complex 3D
shape. The tricuspid annular proximal systolic excursion
(TAPSE) is a well validated and simple measurement which
can be used routinely.17 A TAPSE of ,14 mm is associated
with an adverse prognosis in patients with DCM.18 Measurement of tricuspid regurgitation velocity and pulmonary
artery pressure adds further prognostic information.19
Mitral regurgitation
Left ventricular diastolic dysfunction
Conventional echo-Doppler assessment of LV diastolic dysfunction (transmitral filling pattern) in the assessment of
patients with DCM provides important diagnostic and prognostic information. Increased early filling velocity (E-wave)
and a short deceleration time (‘restrictive filling pattern’,
severe diastolic dysfunction) are associated with severe
haemodynamic impairment, advanced symptoms, and a
poor prognosis13. Moderate (Grade 2, ‘pseudonormal
pattern’) has also been shown to predict a poor outcome
and increased hospitalization.14 Therefore, thorough
Longstanding MR due to leaflet pathology (primary MR) leads
to chronic volume overload of the LV, which may present
with the ‘DCM phenotype’. Conversely, patients with DCM
may develop secondary MR due to varying degrees of
apical tenting of the leaflet tips, annular dilatation, and
ventricular dyssynchrony. The presence of secondary MR
predicts poor outcome.20 There may be patients where it
is difficult to be certain whether the MR is primary or secondary who therefore require detailed assessment of valve
morphology often with transoesophageal echo. Again this
has important management implications as cardiac
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LV dysfunction has long been regarded as the main determinant of clinical symptoms, functional class, and prognosis.7
Accurate quantification of LV function has become the
accepted standard rather than the more traditional
‘eyeball’ estimate used in many echo laboratories,
because many critical clinical decisions rest on the degree
of LV dysfunction, e.g. indications for an implantable defibrillator or resynchronization therapy. The biplane modified
Simpson’s rule is recommended but this also has significant
limitations, relying on good endocardial border definition
which may be suboptimal in up to 15% of patients.8 The
use of contrast agents has been shown to overcome this
problem in the majority of patients. The technique is
highly operator dependent with a standard deviation of
8.5% around the mean EF.9 3D echocardiography has been
shown to improve the reproducibility of LV volume calculation and EF with similar accuracy to MRI.10
The presence of spontaneous echo contrast is often seen
in severely impaired ventricles and should prompt a
careful assessment for thrombus. Again, LV contrast agents
can be used where resolution of the LV apex, and differentiation of thrombus from artefacts, is difficult.11
Determination of LV shape can provide additional prognostic information. The ‘sphericity index’ is the ratio between
the length (mitral annulus to apex in the apical view) and
diameter (mid-cavity level in the short-axis view) of the LV
and predicts functional capacity in patients with LV
dysfunction.12
Ejection fraction (sphericity)
Moderate (pseudonormal) or severe (restrictive filling)
Echocardiography in guiding management in DCM
resynchronization therapy has been shown to improve secondary MR but will be unhelpful in the setting of significant
leaflet disease.21 The therapeutic management of severe
secondary MR is difficult. Chronic volume overload leads to
progressive LV dilatation, dysfunction, and pulmonary hypertension as well as symptomatic deterioration and poor
outcome. Surgical intervention (MV repair or replacement)
is associated with high risk, but may improve symptoms
and outcome. Recently, percutaneous MV repair has been
described. The decision to perform MV repair in the
setting of severe secondary MR in DCM may be influenced
by the presence or absence of LV contractile reserve, i.e.
the prediction of recovery of systolic function. This can be
assessed by stress echocardiography.
Stress echocardiography and left ventricular
contractile reserve
Assessing dyssynchrony in dilated
cardiomyopathy—guiding cardiac
resynchronization therapy
Considerable focus has been placed on the identification of
mechanical dyssynchrony by echocardiography as a method
of refining patient selection for CRT and thus improving
response rates. A large number of techniques have been
described including M-mode, Doppler echocardiography,
and tissue-Doppler imaging (TDI). A detailed description is
beyond the remit of this article; a short description of the
best known of these techniques is given below.
M-mode
In the parasternal short-axis view of the LV at the level of the
papillary muscles, the time interval between peak systolic
inward contraction of the septum and posterior wall represents the septal-to-posterior wall motion delay (SPWMD).
In 20 heart failure patients, a SPWMD of 130 ms predicted
a response to CRT.26 Subsequent analyses have, however,
demonstrated limited predictive value for CRT response27
and highlighted poor feasibility.28
Doppler echocardiography
Patients with severe DCM frequently exhibit a distinctive
pulsed-Doppler LV inflow pattern, with fusion of E- and
A-waves. This results in prolongation of total isovolumic
time (t-IVT), a reduction in effective filling time (LVFT),
and diastolic MR. Atrioventricular dyssynchrony is therefore
indicated by a LVFT of ,40% the cardiac cycle duration.29
The best known parameter assessing isovolumic times is
the myocardial performance index (MPI or Tei index)30
(Figure 3). This measurement reflects the ‘efficiency’ of LV
contraction, as longer isovolumic time reflects increasing
amounts of wasted energy not contributing to ventricular
emptying or filling. Such Doppler measures may have a
role in selecting patients for CRT,31 but appear most useful
in assessing response to therapy.
Interventricular mechanical delay (IVMD) represents the
delay between RV and LV ejection, providing a measure of
interventricular dyssynchrony. It is calculated by measuring
the pre-ejection intervals from the onset of the QRS wave
to the onset of aortic valve and pulmonic valve outflow,
respectively. An IVMD value of 49 ms was reported to be
the only baseline echocardiographic parameter predictive
of improved outcomes post-CRT in the CARE-HF study.32
Tissue-Doppler imaging
Off-line analysis of colour-coded TDI enables analysis of the
timing of contraction of different myocardial regions simultaneously. Measuring the time from QRS onset to peak
Figure 3 (A) Myocardial performance (Tei) index. (A) Tei index is calculated as [a2b/a]. This equals the ratio between the total isovolumic
time (ICT þ IRT) and ejection time. It reflects the efficiency of LV performance, as longer isovolumic time reflects increased amounts of
wasted energy not contributing to ventricular emptying or filling. ICT, isovolumic contraction time; IRT, isovolumic relaxation time, ET, ejection time. (B) Pulsed-wave Doppler of mitral inflow. [a] is measured as the time from the end of the mitral A-wave to the onset of the next
mitral E-wave. (C) Pulsed-wave Doppler of LV outflow. [b] is measured as the time from the onset of flow to the end of flow.
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Stress echocardiography is a useful tool in guiding management in DCM, by identifying the presence or absence of contractile reserve (improvement in wall motion score,
fractional shortening, or EF) during dobutamine infusion
(10–40 mcg/kg/min).22 The presence of contractile reserve
predicts a good response to therapies (including drug treatment and MV repair), whereas absence of contractile
reserve predicts a poor survival rate.23 This has been used
to guide management decisions in the context of need for
cardiac transplantation.24
Dobutamine stress echocardiography is widely used to
identify inducible myocardial ischaemia, viability, and scarring in the assessment of patients with heart failure. Contractile reserve may also help in screening for pre-clinical
DCM in, for example, patients who have been treated for
cancer with anthracyclines.25
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Conclusions
Dilated cardiomyopathy is the most common cardiomyopathy and is associated with a poor prognosis. All
patients with suspected heart failure or LV dysfunction
should undergo a comprehensive assessment by echocardiography, not just to assess LV size and function, but
also to (i) establish the diagnosis of DCM or features of
the ‘DCM phenotype’, (ii) identify associated cardiac
abnormalities such as valve disease, (iii) highlight features
requiring specific therapeutic management, and (iv)
identify high-risk features associated with an adverse
prognosis. Using conventional echocardiography and
Doppler ultrasound in a thorough, comprehensive and
quantitative manner and utilizing recent advances in technology such as tissue-Doppler imaging, strain analysis, and
real-time 3D echocardiography, it is possible to provide
important pathophysiological information that can be
used to guide the optimal clinical management of patients
with DCM.
Conflict of interest: none declared.
References
1. Kopecky SL, Gresh BJ. Dilated cardiomyopathy and myocarditis: natural
history, etiology, clinical manifestations and management. Curr Probl
Cardiol 1987;12:573–647.
2. Glazier JJ, O’Connell JB. Dilated and toxic cardiomyopathy. In:
DiMarco JP, Crawford MH eds, Cardiology. Mosby; 2001.
3. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P et al.
Classification of the cardiomyopathies: a position statement from the
European society of cardiology working group on myocardial and pericardial diseases. Eur Heart J 2008;29:270–6.
4. British society of echocardiography education committee. Guidelines
for chamber quantification. 2008; http://www.bsecho.org. Last accessed
1 May 2008.
5. Kohli SK, Pantazis AA, Shah JS, Adeyemi B, Jackson G, McKenna WJ et al.
Diagnosis of left-ventricular non-compaction in patients with leftventricular systolic dysfunction: time for a reappraisal of diagnostic criteria? Eur Heart J 2008;29:89–95.
6. Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M et al.
for the Angina Pectoris-Myocardial Infarction Investigations in Japan.
Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction.
J Am Coll Cardiol 2001;38:11–8.
7. Likoff MJ, Chandler SL, Kay HR. Clinical determinants of mortality in
chronic congestive heart failure secondary to idiopathic or ischaemic cardiomyopathy. Am J Cardiol 1987;59:634–8.
8. Olszewski R, Timperley J, Cezary S, Monaghan M, Nihoyannopoulis P,
Senior R et al. The clinical applications of contrast echocardiography.
Eur J Echocardiogr 2007;8:S13–23.
9. Otterstad JE, Froeland G, St John Sutton M, Holme I. Accuracy and
reproducibility of biplane two-dimensional echocardiographic measurements of left ventricular dimensions and function. Eur Heart J 1997;
18:507–13.
10. Jenkins C, Bricknell K, Hanekom L, Marwick TH. Reproducibility and accuracy of echocardiographic measurements of left ventricular parameters
using real-time three-dimensional echocardiography. J Am Coll Cardiol.
2004;44:878–86.
11. Thanigaraj S, Schechtman KB, Perez JE. Improved echocardiographic
delineation of left ventricular thrombus with the use of intravenous
second-generation contrast image enhancement. J Am Soc Echocardiogr
1999;12:1022–6.
12. Tischler M D, Niggel J, Borowski DT, LeWinter MM. Relation between left
ventricular shape and exercise capacity in patients with left ventricular
dysfunction. J Am Coll Cardiol 1993;22:751–7.
13. Vanoverschelde JL, Raphael DA, Robert AR, Cosyns JR. Left ventricular
filling in dilated cardiomyopathy: relation to functional class and hemodynamics. J Am Coll Cardiol 1990;15:1288–95.
14. Whalley GA, Doughty RN, Gamble GD, Wright SP, Walsh HJ, Muncaster SA
et al. Pseudonormal mitral filling pattern predicts hospital re-admission
in patients with congestive heart failure. J Am Coll Cardiol 2002;39:
1787–95.
15. Lewis JF, Webber JD, Sutton LL, Chesoni S, Curry CL. Discordance in
degree of right and left ventricular dilatation in patients with dilated cardiomyopathy: recognition and clinical implications. J Am Coll Cardiol
1993;21:649–54.
16. La Vecchia L, Paccanaro M, Bonanno C, Varotto L, Ometto R, Vincenzi
M. Left ventricular versus biventricular dysfunction inidiopathic dilated
cardiomyopathy. Am J Cardiol 1999;83:121–2.
Downloaded from by guest on October 19, 2016
systolic velocity of the basal septal and lateral segments, a
delay of 60 ms predicted an immediate positive haemodynamic response to CRT.33 A four segment model (septal,
lateral, inferior, and anterior) and a delay of 65 ms were
predictive of both clinical and echocardiographic improvement after 6 months of CRT.34 Other investigators have proposed ‘multi-segment models’ of LV dyssynchrony. The ‘Yu
index’ is the most well known of these and describes the
standard deviation of a 12-segment model derived from
sampling six basal and six mid-myocardial segments to
assess LV dyssynchrony.35 Notabartolo et al.36 measured
the time-to-peak systolic velocity in the six basal segments
(septal, lateral, anterior, inferior, anterospetal, and posterior) in 49 patients undergoing CRT. The peak velocity
difference (PVD) was measured as the time difference
between the earliest and latest contracting segment.
A PVD of 110 ms at baseline was predictive of LV reverse
remodelling at the 3-month follow-up.
Although the ability of these dyssynchrony assessments to
predict CRT response had been demonstrated in retrospective single centre studies, they all disappointedly failed to
replicate this success when subjected to a large-scale multicentre prospective analysis.37 The Predictors of Response to
CRT (PROSPECT) trial evaluated 12 blood-pool and tissueDoppler dyssynchrony parameters in 498 patients across
53 countries. The study tested the ability of each index to
predict clinical improvement, and LV reverse remodelling,
and demonstrated unacceptably poor sensitivity and specificity profiles with no single index achieving an area under
the curve in receiver-operating curve analysis of greater
than 0.62. Importantly, this study also highlighted major
limitations to these techniques in terms of their feasibility
and reproducibility. For example, the Yu index could only
be calculated in 50% of subjects, and when successfully
measured, its intra-observer and inter-observer coefficients
of variation were 11.4 and 33.7%, respectively. Paradoxically, these perceived weaknesses of the PROSPECT study
can also be viewed as one of its strengths, as it reflected
‘real-world’ difficulties with accurately making some of
these measurements. The results of this study also serve
as a reminder that all of the methods outlined represent
fundamental trade-offs between spatial and temporal resolution, and this is of particular relevance when dealing with
small amplitude regional wall movement in dilated ventricular cavities.
Newer echocardiographic techniques to evaluate LV dyssynchrony involving real-time 3D echo,38 TDI-derived strain
imaging,39 and 2D-derived speckle tracking strain analysis40
have all been described, and potentially offer solutions to
some of the problems encountered with tissue velocity
imaging. However, in the post-PROSPECT era, the validity
of all proposed indices will be interpreted with a healthy
degree of scepticism until they have been subjected to
further assessment.
D.E. Thomas et al.
Echocardiography in guiding management in DCM
29. Cazeau S, Bordachar P, Jauvert G, Lazarus A, Alonso C, Vandrell MC et al.
Echocardiographic modeling of cardiac dyssynchrony before and during
multisite stimulation: a prospective study. Pacing Clin Electrophysiol
2003;26:137–43.
30. Tei C. New non-invasive index for combined systolic and diastolic ventricular function. J Cardiol 1995;26:135–6.
31. Breithardt OA, Stellbrink C, Franke A, Balta O, Diem BH, Bakker P et al.
Acute effects of cardiac resynchronization therapy on left ventricular
Doppler indices in patients with congestive heart failure. Am Heart J
2002;143:34–44
32. Richardson M, Freemantle N, Calvert MJ, Cleland JG, Tavazzi L. Predictors and treatment response with cardiac resynchronization therapy in
patients with heart failure characterized by dyssynchrony: a predefined analysis from the CARE-HF trial. Eur Heart J 2007;28:1827–34.
33. Bax JJ, Marwick TH, Molhoek SG, Bleeker GB, van Erven L, Boersma E
et al. Left ventricular dyssynchrony predicts benefit of cardiac resynchronization therapy in patients with endstage heart failure before pacemaker implantation. Am J Cardiol 2003;92:1238–40.
34. Bax JJ, Bleeker GB, Marwick TH, Molhoek SG, Boersma E, Steendijk P.
et al. Left ventricular dyssynchrony predicts response and prognosis
after cardiac resynchronization therapy. J Am Coll Cardiol 2004;44:
1834–40.
35. Yu CM, Fung WH, Lin H, Zhang Q, Sanderson JE, Lau CP. Predictors of left
ventricular reverse remodeling after cardiac resynchronization therapy
for heart failure secondary to idiopathic dilated or ischemic cardiomyopathy. Am J Cardiol 2003;91:684–8.
36. Notabartolo D, Merlino JD, Smith AL, DeLurgio DB, Vera FV, Easley KA
et al. Usefulness of the peak velocity difference by tissue Doppler
imaging technique as an effective predictor of response to cardiac resynchronization therapy. Am J Cardiol 2004;94:817–20.
37. Chung ES, Leon AR, Tavazzi L et al. Results of the Predictors of Response
to CRT (PROSPECT) trial. Circulation 2008;117:2608–16.
38. Kapetanakis S, Kearney MT, Siva A, Gall N, Cooklin M, Monaghan MJ. Realtime three-dimensional echocardiography: a novel technique to quantify
global left ventricular mechanical dyssynchrony. Circulation 2005;112:
992–1000.
39. Dohi K, Suffoletto MS, Schwartzman D, Ganz L, Pinsky MR, Gorcsan J 3rd.
Utility of echocardiographic radial strain imaging to quantify left ventricular dyssynchrony and predict acute response to cardiac resynchronization therapy. Am J Cardiol 2005;96:112–6.
40. Suffoletto MS, Dohi K, Cannesson M, Saba S, Gorcsan J 3rd. Novel speckletracking radial strain from routine black-and-white echocardiographic
images to quantify dyssynchrony and predict response to cardiac resynchronization therapy. Circulation 2006;113:960–8.
Downloaded from by guest on October 19, 2016
17. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricular
function using two-dimensional echocardiography. Am Heart J 1984;
107:526–31.
18. Ghio S, Recusani F, Klersy C, Sebastiani R, Lauisa ML, Campana C et al.
Prognostic usefulness of the tricuspid annular plane systolic excursion
in patients with congestive heart failure secondary to idiopathic or
ischaemic dilated cardiomyopathy. Am J Cardiol 2000;85:837–42.
19. Enriquez-Sarano M, Rossi A, Seward JB, Bailey KR, Tajik AJ. Determinants
of pulmonary hypertension in left ventricular dysfunction. J Am Coll
Cardiol 1997;29:153–9.
20. Donal E, DePlace C, Kervio G, Bauer F, Gervai R, Leclerq C et al. Mitral
regurgitation in dilated cardiomyopathy: value of both regional left ventricular contractility and dysynchrony. Eur J Echocardiogr 2009;10:
133–8.
21. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D,
Kappenberger L et al. Cardiac Resynchronisation-Heart Failure
(CARE-HF) Study Investigators The effect of cardiac resynchronisation
therapy on morbidity and mortality in heart failure. N Engl J Med 2005;
352:1539–49.
22. Kitaoka H, Takata J, Yabe T, Hitomi N, Furuno T, Doi YL. Low dose dobutamine stress echocardiography predicts the improvement of left ventricular systolic function in dilated cardiomyopathy. Heart 1999;81:523–7.
23. Pratali L, Picano E, Otasevic P, Vigna C, Palinkas A, Cortigiani L et al.
Prognostic significance of the dobutamine echocardiography testing idiopathic dilated cardiomyopathy. Am J Cardiol 2001;88:1374–8.
24. Costanzo MR, Augustine S, Bourge R, Bristow M, O’Connell JB, Driscoll D
et al. Selection and treatment of candidates for heart transplantation.
Circulation 1995;92:3593–612.
25. Klewer SE, Goldberg SJ, Donnerstein RL, Berg RA, Hutter JJ Jr. Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term
survivors of childhood cancer. J Am Coll Cardiol 1992;19:394–401.
26. Pitzalis MV, Iacoviello M, Romito R, Massari F, Rizzon B, Luzzi G et al.
Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony. J Am Coll Cardiol 2002;40:1615–22.
27. Marcus GM, Rose E, Viloria EM, Schafer J, De Marco T, Saxon LA et al.
Septal to posterior wall motion delay fails to predict reverse remodeling
or clinical improvement in patients undergoing cardiac resynchronization
therapy. J Am Coll Cardiol 2005;46:2208–14.
28. Bleeker GB, Schalij MJ, Boersma E, Holman ER, Steendijk P, van der
Wall EE et al. Relative merits of M-mode echocardiography and tissue
Doppler imaging for prediction of response to cardiac resynchronization
therapy in patients with heart failure secondary to ischemic or idiopathic
dilated cardiomyopathy. Am J Cardiol 2007;99:68–74.
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